streptomycin

Indications

• used in combination therapy for tuberculosis
• used in combination therapy for streptococcal or enterococcal endocarditis
• mycobacterial infections
• plague
• tularemia
• brucellosis
• chancroid
• donovanosis

Contraindications

• avoid in patients >= 60 years of age

pregnancy category = d

safety in lactation = ?

Dosage

• adults:
  • tuberculosis:
    • 15 mg/kg/day divided every 12 hours
    • not to exceed 1 g/day
    • generally discontinued after 2-3 months or sooner if cultures become negative
  • enterococcal endocarditis
    • 1 g every 12 hours for 2 weeks
    • 500 mg every 12 hours for 4 weeks in combination with penicillin
  • streptococcal endocarditis
    • 500 mg-1 g every 12 hours for 1 week
    • if > 60 years of age, give 500 mg every 12 hours for 2 weeks
  • tularemia: 1-2 g/day divided every 12 hours for 7-14 days or until patient is afebrile for 5-7 days
  • plague: 2 g/day divided every 12 hours for a minimum of 10 days
• children
  • tuberculosis
  • 20-30 mg/kg/day
  • not to exceed 1 g/day
  • generally discontinued after 2-3 months or sooner if cultures become negative
• IM administration only into large muscle mass

Injection: 400 mg.mL (2.5 mL)

Dosage adjustment in renal failure

Table

creatinine clearance	dosage
50-90 mL/min	50% every 24 hours
10-50 mL/min*	every 24-72 hours
< 10 mL/min	every 72-96 hours
> 80 mL/min	15 mg/kg every 24 hours
60-80 mL/min	12 mg/kg every 24 hours
40-60 mL/min	7.5 mg/kg every 24 hours
30-40 mL/min	4 mg/kg every 24 hours
20-30 mL/min	7.5 mg/kg every 48 hours
10-20 mL/min	4 mg/kg every 48 hours
< 10 mL/min#	3 mg/kg every 48 hours

* same dose for continuous arteriovenous hemofiltration

# 3 mg/kg after hemodialysis

Pharmacokinetics

• not absorbed from GI tract; must be given parenterally
• peak serum concentration 1 hour after IM dose
• serum concentration of 40 ug/mL with does of 15 mg/kg
• most strains of M. tuberculosis inhibited by 8 ug/mL
• good tissue penetration, but CSF penetration only with meningeal inflammation
• removed by hemodialysis
• 1/2life 2-3 hours (30-80 hours ESRD)

elimination via kidney

elimination by hemodialysis = +

Monitor

• streptomycin in serum
  • therapeutic range:
    • Peak: 10-20 ug/mL
    • Trough: < 5 ug/mL
• hearing
• renal function tests

Antimicrobial activity

• Mycobacterium avium complex
• Enterobacter
• gram-negative bacteria
  • Haemophilus
    • Haemophilus influenzae
  • Escherichia coli
  • Klebsiella
  • Proteus

Adverse effects

• not common (1-10%)
  • nephrotoxicity, neurotoxicity, ototoxicity (auditory & vestibular)
• uncommon (< 1%)
  • rash, drug fever, headache, paresthesia, tremor, nausea/vomiting, eosinophilia, arthralgia, anemia, hypotension, difficulty breathing, drowsiness, weakness
• other
  • ototoxicity
    • tinnitus
    • hearing loss
    • vertigo
    • vestibular toxicity may occur up to 2-3 months after stopping drug
  • adverse effects dose-related & increased with age

• drug adverse effects of aminoglycosides

Mechanism of action

• bactericidal against M. tuberculosis in an alkaline environment

More general terms

• aminoglycoside antibiotic
• anti-tuberculous agent

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?